*11.1.1. Reverse transcriptase inhibitors*

Fanconi syndrome [177-179, 184]. Additionally, its use in PrEP is well tolerated, and the occurrence of headache, nausea, vomiting, abdominal pain, and weight loss may occur infrequently [177-179]. Nausea and vomiting affects about one in six patients at the beginning of the treatment, but these effects often reduce in the first month [177]. Although the use of

**Table 5.** Clinical trials with TDF/FTC (Truvada®) for pre-exposure prophylaxis (PrEP)(GRADE Criteria). Note: Grade

moderate=further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate;low= further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate; very low=any estimate of effect is very uncertain. \*All trials in this table

**trial\* Sample size Limitations Evidence**

Adherence High

Minimal High

Minimal High





Minimal High

Low

Low

Low

Placebo (n=199) -High loss to follow-up Moderate

concerns

drug

in both


TDF and TDF/FTC arms

Placebo (n=1248)

Placebo (n=199)

TDF(n=1589) TDF/FTC (n=1583) Placebo (n=1589)

Placebo (n=1058)

Placebo (n=467)

TDF(n=1007) TDF/FTC (n=1003) Placebo (n=1009)

Placebo (n=1207)

quality rating: high=further research is very unlikely to change our confidence in the estimate of effect;

**Study**

Among men who have **sex with men**

Among heterosexual men

Partners PrEP(n=4758) Phase lll trial

Among heterosexual Women

**and women**

VOICE(n=3019)

Among injection drug users

**Clinical**

148 Trends in Basic and Therapeutic Options in HIV Infection - Towards a Functional Cure

iPrEX trial (n=2499) Phase lll trial TDF/FTC (n=1251)

US MSM Trial(n=400) Phase ll trial TDF/FTC (n=201)

TDF2(n=1219) Phase ll trial TDF/FTC (n=201)

FEM-PrEP(n=2120) Phase lll trial TDF/FTC (n=1062)

West African(n=936) Phase ll trial TDF (n=469)

Phase llB trial

BTS(n=2411) Phase lll trial TDF (n=1204)

were randomized, double-blind, prospective clinical trials.

Reverse transcriptase inhibitors are antiretroviral with recognized efficacy and safety in the treatment of HIV-1 infection and prevention of mother-to-child HIV-1 transmission. This class of drugs has allowed the formulation of topical microbicide less toxic and more effective [194]. The nucleotide reverse transcriptase inhibitor tenofovir was the first antiretroviral drug to safely demonstrate in animal models both pre-exposure and post-exposure prophylaxis as proof-of-concept against the sexual transmission of HIV-1 [195, 196]. Two other compounds of class NNRTIs being studied as topical microbicides to prevent HIV-1 infection, are the TMC120 and UC781. Preclinical or clinical testing of these compounds as potential topical microbicides have several features in common, and both compounds show minimal systemic absorption, and good safety profiles in animal studies [200, 201]. *In vitro*, TMC120 and UC781 prevent cell-free and cell-associated virus from infecting co-cultures of monocyte-derived dendritic cells and T cells [202-204].

#### *11.1.1.1. Tenofovir*

Tenofovir is active as a diphosphate, rather than a triphosphate, which does not act via HIV DNA chain termination, coupled with the limited phosporylation ability of macrophages. This explains why the drug might be effective in macrophages and other non-dividing cells [197, 198]. Based on the animal studies and with an appreciation for tenofovir's relatively high barrier to resistance compared with other reverse transcriptase inhibitors [196], the compound became the first antiretroviral drug to be assessed as a VM in a clinical trial. In a phase I study (HPTN 050), 0 3% and 1% vaginal tenofovir gel, formulated as a diphosphate, was used once or twice daily for 14 days by HIV-1 infected and uninfected women. The gel was found to be safe, well tolerated, and acceptable to participants [199].



Note: NNRTI=non-nucleoside reverse transcriptase inhibitor; STI=sexually transmitted infection; SHIV=chimeric simian/ human immunodeficiency virus;HSV=herpes simplex virus.

\*NCT number: Clinical trials.gov website :http://www.clinicaltrials.gov.

**Table 6.** Specific and non-specific microbicides agents for prevention HIV-infection.
